Abstract
Asthma is a frequent disease, mainly characterized by airway inflammation, in which drug therapy is crucial in its management. The potential of pharmacogenomics testing in asthma therapy has been, to date, little explored. In this review, we discuss pharmacogenetic factors affecting asthma treatment, both related to drugs used as controller medications for regular maintenance, such as inhaled corticosteroids, anti-leukotriene agents, long-acting beta-agonists, and the new biologic agents used to treat severe persistent asthma. In addition, we discuss current pharmacogenomics knowledge for rescue medications provided to all patients for as-needed relief, such as short-acting beta-agonists. Evidence for genetic variations as a factor related to drugs response has been provided for the following genes and groups of drugs: Inhaled corticosteroids: FCER2; anti-leukotriene agents: ABCC1, and LTC4S; beta-agonists: ADRB2. However, the following genes require further studies confirming or rejecting association with the response to asthma therapy: ADCY9, ALOX5, ARG1, ARG2, CRHR1, CRHR2, CYP3A4, CYP3A5, CYSLTR1, CYSLTR2, GLCCI1, IL4RA, LTA4H, ORMDL3, SLCO2B1, SPATS2L, STIP1, T, TBX21, THRA, THRB, and VEGFA. Although only a minority of these genes are, at present, listed as associated with drugs used in asthma therapy, in the Clinical Pharmacogenomics Implementation Consortium gene-drug pair list, this review reveals that sufficient evidence to start testing the potential of clinical pharmacogenomics in asthma therapy already exists. This evidence supports the inclusion in pilot pharmacogenetics tests of at least four genes. Hopefully these tests, if proven useful, will increase the efficiency and the safety of asthma therapy.
Highlights
Asthma is an important and frequent disease, mainly characterized by airway inflammation
It is interesting to note that among the huge number of guidelines published by the Clinical Pharmacogenetics Implementation Consortium (CPIC R ) to optimize drug therapy based on pharmacogenomics tests, none are related to the drugs used in asthma therapy (Caudle et al, 2014)
Some clear clusters do exist, but some genes, though putatively affecting response to diverse types of drugs, are related
Summary
Asthma is an important and frequent disease, mainly characterized by airway inflammation. Drugs used in asthma treatment are classified into two main groups. The second group is classified as relievers or rescue drugs: These drugs are prescribed for relief of symptoms as-needed, for example when exacerbations or aggravation of asthma exist [Global Initiative for Asthma (GINA), 2018]. Despite improvements in treatment and the implementation of these guides, adequate control of symptoms is not achieved for more than half of patients (Chapman et al, 2008). An important group of causes explaining different responses to asthma medications is related to the expression of drug targets and/or enzymes involved in drug biodisposition, often due to genetic variability (Ortega et al, 2015). We analyze the above-mentioned group of causes, that is, the different polymorphisms affecting drug target molecules, or affecting drug metabolism and causing interindividual differences in the response to asthma treatment and evolution. Details of the putative associations of these genes with response to asthma therapy are provided below
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